Enterobacteria similar to the bacteria used to inoculate mice against cockroach allergens. Source: CDC Public Health Image Library (PHIL)

According to new research recently published in the Journal of Immunology, there’s a good chance that the answer is yes.1 Eager to hop into the biologics and immunotherapeutic crazes, researchers successfully immunized a group of neonatal mice against a common allergen: cockroach-borne enterobacteria. Following inoculation, researchers were able to isolate immunoglobulins which were specific to the enterobacteria that they’d administered. This confirms that the mice would grow up to be immune to the sensitization which characterizes allergy and supports the growing body of research on the matter.2 The new research was possible without any sophisticated vaccine design software, though there’s reason to believe that future efforts won’t be.

It’s clear that the future of allergy medicine will include similar vaccines to head off as many common human allergies as possible. Unlike in traditional vaccine development, which seeks to elicit immunity to a single pathogen, vaccines against human allergies will be far more complex and require a much broader and calibratable range of immune responses after vaccination. There are a number of other compelling factors which indicate that allergy vaccine development will require robust information management systems that current vaccine development platforms currently can’t provide.

Immunotherapy for Mice

In the new study, researchers were able to lean on prior research which traced the pathogenesis of murine cockroach allergy to a single enterobacterial strain. Like all bacteria, the MK7 enterobacteria used in the study is characterized by the glucan motifs on its capsule. As it turns out, these glucan motifs are the point of interface between the enterobacteria and the mouse’s immune system, meaning that they’re the allergy antigen. Once researchers identified the antigen, they could isolate it and deliver it to neonatal mice as a vaccine.

Figuring out whether the inoculation technique had worked on the mice was as simple as assaying the mice for their generation of anti-enterobacterial glucan motif antibodies. For the researchers to declare their experiment a success, they only needed to find one isotype of glucan-specific antibodies—which they did.

Immunologists can probably envision exactly how easy this test would be for a single antigen; one afternoon of running an ELISA would be more than sufficient. In a real world application, generating just one isotype of allergen-specific antibodies and looking for just one level of antibody specificity might not be enough, however.

Though some allergies are characterized by single allergens, most allergies have a plethora of antigens which trigger an immune response. There’s some evidence that allergen-specific immunotherapy can benefit from using a mixture of antigens—sometimes a very large mixture—to inoculate the host.3

There’s still a paucity of data on exactly how many antigens are needed within a vaccine mixture to make it effective for a given allergy, but it’s clear that at least a few different antigens are needed to successfully prevent an allergic reaction to encountering one of the antigens.4 A small and manageable data set of vaccine efficacy containing one antigen and one specific antibody rapidly spirals out of control multiplicatively with the inclusion of multiple antigens and antibodies with multiple overlapping specificities.

The New Allergy Immunotherapy Landscape

Let’s take a look at the data set required to generate the murine vaccine against enterobacterial glycan motifs. To successfully design their vaccine and test it, researchers needed:

  • Knowledge of the cockroach allergy pathogenesis and antigen
  • Isolation of the sole allergy antigen
  • Raising of experimental and control mouse groups
  • Confirmation of one antigen-specific antibody generated from one of the mice in the experimental group
  • Confirmation of the experimental group’s immunity by challenge with antigen

But as far as allergies go, the murine cockroach allergy is traceable to a single antigen. Furthermore, researchers raise mice in sterile environments, guaranteeing that all their encounters with allergens are known and under control. There’s no need to assay the mice for prior exposure to antigens. Human subjects have many more unanswered questions that researchers need to know before even starting to test their vaccine.

For allergies more relevant to human health, like hay fever, there are dozens or perhaps even hundreds or thousands of different antigens. Furthermore, many human allergies have more complex pathogenesis due to behavioral factors and highly variable environmental factors.5

Making the jump from single-antigen immunotherapy to poly-antigen immunotherapy in human subjects will require the following information and the answers to the following questions:

  • Knowledge of at least a subset of allergy antigens
  • Knowledge of at least the initiating mechanism of the target allergy pathogenesis
  • Isolation of the known allergy antigens
  • Knowledge of sensitization cofactors in the environment
  • Formulation of known antigens into a vaccine
  • Formation of experimental and control patient groups in a clinical study
  • Knowledge of each patient’s allergic status; has the patient already been sensitized to one or more of the antigens without realizing it?
  • Titration of vaccine dosage
  • Confirmation of at least one specific antibody for each antigen
  • Examination of antibody isomorph multi-specificity, if any
  • Examination of antibody impact on cofactors for other allergies or vice versa; does the vaccine provide immunity to non-targeted allergies?
  • Examination of minimal avidity antibody isomorphs in relation to patient genetic information; does a certain genetic profile correlate to faulty antibody production and thus allergy development even when vaccinated?
  • Ruling out inverse effect of vaccine; does over-sensitization occur as a result of the vaccine’s infusion of antigens?
  • Assessing patient symptomatology in response to challenge with antigen after confirmation of specific antibody generation; are the generated antibodies sufficient to provide functional immunity to the antigen?

Designing the Vaccines of the Future

These factors are just the start of human-targeted allergen-specific immunotherapy and don’t even include rudimentary safety testing and the nuances of patient genetics. It’s clear that the two-dimensional data landscape of prior allergy targeted immunotherapies has come to an end, and future inquiry will lean heavily on antigen diversity to guarantee vaccine efficacy.

Researchers aren’t currently equipped with the data management systems that they’ll need to handle designing vaccines that require so many moving parts to inoculate and verify inoculation. Thankfully, there is an information processing and collaboration platform which researchers can use to design the immunotherapeutic allergy vaccines of the near future.  

Designed to Cure is the information technology platform for creating vaccines that use thousands of antigens to inoculate patients against allergies. Designed to Cure enables your team to characterize thousands of proteins, conduct in vivo studies, and continuously add to your data based understanding of allergy pathogenesis. Contact us today to find out how you can use Designed to Cure to jump into the allergy immunotherapy revolution.

  1.  “Pulmonary alpha-1,3-Glucan-Specific IgA-Secreting B Cells Suppress the Development of Cockroach Allergy.” October 2016, http://www.jimmunol.org/content/197/8/3175
  2.  “Sensitization to cat and dog allergen molecules in childhood and prediction of symptoms of cat and dog allergy in adolescence: A BAMSE/MeDALL study.” May 2015, http://www.sciencedirect.com/science/article/pii/S0091674915015742
  3. “The use of single versus multiple antigens in specific allergen immunotherapy for allergic rhinitis: review of the evidence.” February 2014, http://journals.lww.com/co-allergy/Abstract/2014/02000/The_use_of_single_versus_multiple_antigens_in.5.aspx
  4. “Clinical benefit of component-resolved diagnosis in Japanese birch-allergic patients with a convincing history of apple or peach allergy.” October 2016, http://www.sciencedirect.com/science/article/pii/S0385814616304527
  5. “Allergen-specific immunoprophylaxis: Toward secondary prevention of allergic rhinitis?” February 2014, http://onlinelibrary.wiley.com/doi/10.1111/pai.12200/full